Can composite packaging and selective enamel etching affect the clinical behavior of bulk-fill composite resin in posterior restorations? 24-month results of a randomized clinical trial

Abstract Objectives This is a double-blind, split-mouth, randomized clinical study that aims to evaluate the influence of bulk-fill composite packaging presented in syringes (BSy) and capsules (BCa), and the effect of selective enamel etching (SEE) on the clinical performance of class I and II bulk-fill resin composite restorations after 24 months. Methodology A total of 295 class I or class II restorations were performed on 70 patients. One universal adhesive was applied in all restorations. SEE was used in 148 restorations and self-etching mode (SET) in 147 restorations. After the adhesive application, cavities were restored with Filtek Bulk-fill Posterior Restorative in syringes (BSy), Filtek One Bulk-fill in capsules (BCa), or Filtek Supreme Ultra in syringes with the incremental technique (In). All restorations were evaluated using the FDI criteria after one week and after six, 12, and 24 months. Kaplan-Meier survival analysis and Pearson’s Chi-square test were used (α=0.05) for statistical analysis. Results After 24 months, 62 patients were evaluated and four restorations were lost due to fracture (one for SEEBSy, two for SEEIn, and one for SETIn). No significant differences in the fracture and retention rate were found between groups (p>0.05). SEE showed significantly fewer marginal adaptation defects than SET (p<0.05). BCa and BSy groups showed fewer marginal discrepancies compared to In (p<0.05). Restorations performed with BCa showed less color mismatch than BSy or In (p<0.05). Conclusion Although all restorations exhibited satisfactory clinical performance after 24 months of clinical service, the clinical behavior of class I and II restorations’ improved when performed with a bulk-fill composite in capsules, mainly when associated with a universal adhesive applied with SEE.


Introduction
For many years, the incremental technique has been the most suitable method for restoring teeth using composite resin, with increments of up to 2 mm in thickness. This technique facilitates a proper light curing of the composite and reduces the stress generated by polymerization shrinkage. 1  The first bulk-fill composite resins introduced to the market were flowable bulk-fill or low-viscosity bulk composite resins, whose effectiveness has been evaluated and approved in long-term studies. 6,7 Regular bulk-fill resins that were later introduced to the market still lack further scientific evidence, as few studies have been conducted to evaluate occlusal or occlusal-proximal restorations performed with bulk-fill resins with 24 or more months of clinical follow-up. [8][9][10][11][12][13] On the other hand, several commercial composite resins were recently launched in single doses (capsules) in addition to the traditional presentation in syringes. According to the manufacturers, this new presentation seems to help clinicians with infection control during restorative procedures, apart from being easily handled with a dispenser and being less time-consuming because it does not require using a spatula to pick a portion of the material from the syringe, which is necessary in some cases.
However, a recently published study 5 showed no Universal adhesive systems are another group of materials that have been developed aiming to facilitate and speed up the performance of adhesive restorative procedures due to their versatility. 14 These materials have been extensively evaluated in laboratory and clinical research, usually in non-carious cervical lesions, and its results seem very promising. [15][16][17] However, only a few medium-term evaluations were performed on class I or II occlusal restorations using these universal adhesive systems combined with bulkfill composites, 12,18,19

Participants recruitment
Patients were recruited in the order in which they appeared for screening sessions in the Fluminense Federal University dental clinics, thus forming a sample of convenience. Two calibrated dental residents (C.T. and F.C.) recruited the patients. The calibration was performed before the start of the screening sessions and teeth selection. In two consecutive days, the investigators clinically and radiographically evaluated 10 teeth with class I and II lesions. After the evaluation, inter-examiner and intra-examiner agreements were estimated, and a score of at least 85% was required for dentists to be considered calibrated. 21

Eligibility criteria
Participants had to be in good general health, be at least 18 years, have an acceptable oral hygiene level according to the Simplified Oral Hygiene Index (OHI-S), 22 have at least three posterior teeth with a carious lesion that required restoration or deficient posterior restoration in need of replacement and repair that is not feasible due to deep caries or exposed dentin not accessible for repair, generalized major gaps or irregularities, partial or complete loss of restoration, and/or multiple fractures (more than half of the restoration), that cause several adverse effects, including pain. 23 Patients with severe or chronic periodontitis (teeth with probing pocket depth more than 4 mm with bleeding on probing and clinical attachment loss more than 3 mm in more than four teeth 24 were excluded.
Participants with known allergies to resin-based materials or any other material used in this study, pregnant or breastfeeding women, patients using anti-inflammatories, analgesics, or psychotropic drugs within 15 days of the restorative procedure were also excluded.
Characteristics of the teeth/cavities to be included The teeth intended for restoration had to be in occlusion with their natural antagonist tooth and adjacent teeth. To identify occlusal interferences in the intercuspal position and in the lateral movements, articulating paper was used. If the tooth presented an occlusal interference, an occlusal adjustment was performed. Teeth requiring endodontic treatment (evaluated by radiography and by the cold pulpal sensitivity test [Roeko-Endo-Frost, Coltène / Whaledent, Langenau, Germany]) were excluded.
The dental cavities had to be class I or class II (involving the occlusal surface) of a depth greater than 2 mm, evaluated by means of a bitewing radiograph and ruler in vital teeth. Following the American Dental Association Caries Classification System (ADA CCS), the extension of the included carious cavities had to be moderate (enamel breakdown with noncavitated carious dentin) or advanced (full cavitation through the enamel and dentin clinically exposed).
Radiographically, for class II lesions, the radiolucency had to be extended to the outer one-third of dentin, into the middle one-third of dentin, or into the inner one-third of dentin. 25

Sample size calculation
The average of annual failure rate of bulk-fill composite resin restorations in randomized clinical trials was 2.5%. 6,26 Therefore, the overall success rate of bulk-fill composite restorations would be approximately 95% after two years of clinical service.
With an α of 0.05, a power of 90%, and a two-sided test, the minimal sample size was 44 restorations in each group to detect a difference of 25% between groups. However, considering the risk of patient losses intrinsic to randomized clinical trials, we chose to

Randomization, allocation, and blinding
Initially, 377 teeth were evaluated, but 59 were excluded because of the reasons described in Figure   1. After the screening sessions, 81 patients were selected and scheduled to perform the restorations. A total of 318 teeth, treated as research subjects, were randomized in blocks of six to ensure an equal number of restorations in each of them. The randomization process was performed using a free program available at http://www.sealedenvelope.com by a researcher uninvolved in any experimental phases (R.Ñ.).
The randomization list was numbered consecutively and was individually placed in opaque sealed envelopes opened on the day of the restorative intervention to prevent disclosure of the randomization scheme. The operator who conducted the interventions was not blinded. However, participants and examiners were kept blind to the group allocation during examinations.

Baseline characteristics of the selected teeth
The characteristics of each patient (gender, age) and the teeth intended for restoration (tooth type, arch, cavity type, presence of spontaneous sensitivity before restoration, number of restored surfaces, and restoration reason) were evaluated and recorded by four trained and calibrated operators before the placement of the restorations. These operators were also involved in the selection of participants and conduct of the restorative procedures ( Table 1).
The four operators (C.T., E.A., L.L., and S.M.) were dentists with more than five years of clinical Intervention: restorative procedure The patients received instructions for oral hygiene and dental prophylaxis of the tooth surface with pumice and water in a rubber cup, followed by rinsing and drying, with the aim of removing any remaining dental plaque. The proper shade of the resin composite was determined using a shade guide (Vita Classical, Vita Zahnfabrik, Bad Säckingen, Germany) before the restorative procedures. Local anesthesia was applied with a 3% mepivacaine solution (Mepisv 3%, NovaDFL, Rio de Janeiro, Brazil) and rubber dam isolation was performed. The cavity design was defined by the extension of carious tissue or removal of the defective restoration, and it was performed as conservatively as possible. It did not involve any cusps and all gingival margins had sound enamel.
The defective restorations were removed using a spherical diamond bur (# 1013; KG Sorensen, Barueri, Brazil) mounted in a high-speed handpiece with airwater spray. After removing the defective restorations, in the case of primary caries or the necessity of caries removal, after removing the failure restorations, the criteria used for the removal of carious tissue was selective, maintaining the affected dentin layer. This procedure was performed using hand instruments and slow-speed tungsten carbide burs (# 2 and 4; KG Sorensen, Barueri, Brazil). Bevels were not performed in cavity walls to avoid unnecessary loss of dental tissue. After cavity preparation, the width, length, and depth of occlusal and proximal boxes were measured using a periodontal probe (# 6 Satin Steel Handle, mm, Hu-Friedy, Chicago, IL, USA) and recorded. The deepest measure was used as reference to determine the number and thickness of the increments needed to fill the cavity with the composite resins.

Variable
Group ( Restoration change for other reasons 10 9 9 14 7 9 58 (*) SEEBSy, self-etch with selective enamel etching and bulk in syringe; SETBSy, self-etch and bulk in syringe; SEEBCa, self-etch with selective enamel etching and bulk in capsule; SETBCa, self-etch and bulk in capsule; SEEIn, self-etch with selective enamel etching and incremental composite; SETIn, self-etch and incremental composite. For the In group, each increment of composite resin was removed from the compule, shaped into a ball using the right thumb and index finger, and then placed in the cavity with a resin spatula. The operators wore new and clean gloves immediately before the restorative procedure to avoid contamination with saliva or carious tissue removal. Gloves and spatulas were cleaned with 70% alcohol and dried with absorbent paper between each incremental layer. In the BSy groups, one 4-mm-thick layer was placed at the bottom of the cavity, as described in the In group. However, for BCa groups, the material was dispensed using the Mark IIIP™ Speed Slot Syringe Once the restorative procedures were finished, the rubber dam was removed, occlusal adjustments were performed using articulating paper (Bausch, Nashua, NH, USA), and premature contacts were removed using fine and extra-fine diamond points (# 1190F and # 1190FF, KG Sorensen). Restorations were polished with spiral discs (Sof Lex spiral, 3M Oral Care) and proximal contacts were checked with dental floss and adjusted with sanding strips (3M Oral Care) if necessary. At the end of the restorative procedure, each patient was scheduled for the subsequent evaluation (1 week) and then for the next follow-ups (6-, 12-, and 24-months). Therefore, the restorations in each patient had a particular scheduled time.

Clinical evaluation
The postoperative sensitivity was evaluated over seven days, by the patients themselves, using two scales. A numerical rating scale (NRS), with five categories of how much sensitivity each tooth had [0 (none), 1 (mild), 2 (moderate), 3 (considerable), or 4 (severe)], and a Visual Analogue Scale (VAS), a 100 mm long straight line with scores 0 (no sensitivity) and 100 (unbearable pain) at each end. The patient was instructed to mark where their postoperative sensitivity was located along this spectrum. The patient got a form for each restored tooth, with the two scales replicated seven times, and was instructed to mark the specific day of the record of sensitivity and indicate whether it was spontaneous or stimulated.
In the case of stimulated sensitivity, they were asked to indicate the cause of the sensitivity (i.e., chewing, heat, cold, or another stimulus). 5 Two experienced and calibrated examiners (L.P. and R.B.), not involved in the restorative procedures, starting the evaluation. 21 Each examiner used a standardized paper report form at each recall time, so they were kept blind to previous evaluations during the follow-up recalls.
The primary outcome was fracture and retention, and the secondary outcomes were marginal adaptation, proximal contact quality (for class II restorations), patient's perception, marginal staining, color match, anatomic form, postoperative sensitivity, and recurrence of caries. The proximal contact and cervical adaptation for class II restorations were evaluated using dental floss and bitewing radiography when Fillers: Combination of a nonagglomerated/non-aggregated 20 nm silica filler, a non-agglomerated/ nonaggregated 4 to 11 nm zirconia filler, an aggregated zirconia/silica cluster filler (comprised of 20 nm silica and 4 to 11 nm zirconia particles); 78.5 wt%, 66.3 vol%.

Photoinitiator: Camphorquinone
Insert in the cavity oblique increases of up to 2 mm in thickness, and light-cure each area of the surface of the restoration with a dental curing light appliance light power of 1200 mW/cm 2 for 20 s.

Photoinitiator: Camphorquinone
Insert in the cavity bulk increases of up to 5 mm in thickness, and light-cure each area of the surface of the restoration with a dental curing light appliance light power of 1200 mW/cm 2 for 40 s.

Photoinitiator: Camphorquinone
Insert in the cavity bulk increases of up to 5 mm in thickness, and light-cure each area of the surface of the restoration with a dental curing light appliance light power of 1200 mW/cm 2 for 40 s.  examiners considered it necessary. Variables were ranked following the FDI criteria categories: clinically very good, clinically good, clinically sufficient/ satisfactory, clinically unsatisfactory but repairable, and clinically poor where replacement is required.
Both examiners evaluated all restorations once and independently, reaching a consensus before the participant was dismissed.
All restorations scored as clinically unsatisfactory or poor by FDI criteria at one recall were accounted as a cumulative failure at the next follow-up evaluation.
Each failed restoration was replaced with a new composite resin restoration. 28 These new restorations were not included as part of the study for further evaluation. Participants' restorations whose evaluation was not possible to perform were considered lost to follow-up.

Statistical analysis
The statistician was blinded to the type of study groups. The statistical analysis followed the intention- The restorative procedures were implemented exactly as planned, and no modification was conducted.
All baseline details regarding the research subjects and characteristics of the restored cavities were described in Table 1.  which was fracture and retention ( Figure 4). Table 4 depicts the paired comparisons among the six research groups as the hazard ratios. The fact that the 95%CI interval of the hazard ratio crosses the null value of 1 means that none of the paired groups showed any significant difference.

Proximal contact quality
No restoration showed any problem regarding proximal contact according to the FDI criteria after six, 12, and 24 months of clinical evaluation (p=1.00; Table 2).

Patient's perception
Only one restoration for SEEIn presented minor problems regarding the patient perception at the 24-month follow-up according to the FDI criteria (  A  40  35  42  34  29  29   B  6  11  --7  12 13

Marginal staining
After 24 months of clinical evaluation, 18 restorations (two for SEEBSy; two for SETBSy; one for SEEBCa; and one for SETBCa, seven for SEEIn; and five for SETIn) showed minor marginal staining according to the FDI criteria (Table 2). Regarding restorations made with SEE or SET, no significant difference was found between groups at 24-month recall (p>0.05; Table 2). When different composites were compared, a significant and smaller number of restorations with marginal staining was observed in restorations performed with bulk-fill in capsules and in syringes when compared to restorations performed with the incremental technique after a 24-month recall (p=0.002). No significant difference was detected in any other comparison at the 6-and 12-month recalls (p>0.05; Table 2).

Color match
At the 24-month follow-up, 19 restorations showed minor discrepancies in the color match (five for SEEBSy; four for SETBSy; five for SEEIn; and five for SETIn) according to the FDI criteria (    Table 2).

No significant difference was detected in any other
comparison of groups at the 6-and 12-month recalls (p>0.05; Table 2).

Anatomic form
At the 24-month follow-up, one restoration for SEEBSy presented minor anatomic form problems according to the FDI criteria (Table 2). No significant difference was detected between any pair of groups at the 6-, 12-, and 24-month follow-ups (p=1.00; Table 2).

Post-operative (hyper-) sensitivity
One restoration for SEEIn presented unacceptable post-operative sensitivity after 12 months according to the FDI criteria (Table 2) and had to be replaced. The patient did not return to the 24-month recall. None of the remaining restorations showed post-operative sensitivity after 24 months of clinical evaluation ( Table   2). No significant difference was detected between any pair of groups at 24-month follow-ups (p=1.00; Table 2).

Recurrence of caries
No restorations had a recurrence of caries at the 1-week evaluation or at the 6, or 12-month recall according to the FDI criteria (p=1.00; Table 2).
One restoration for SEEIn showed a recurrence of caries after 24 months according to the FDI criteria (p=0.3812; Table 2) and had to be replaced after this period.

Discussion
In this study, some clinical parameters of the with previous literature. 8,12,[30][31][32][33] The studied composites' low fracture rate, as well as the satisfactory anatomic form and proximal contact, could be explained by their larger amount of filler. Moreover, the materials contain additional zirconia filler, and zirconia/silica fillers (2.5 and 5.0 wt%) replace those of glass, improving some mechanical properties such as flexural strength and fracture resistance. 34   It was reported that some baseline characteristics of cavities could affect the survival of posterior restorations, such as cavity extensions (class I or II). 50 In fact, a recent study showed that "larger cavities" statistically suffered more failure than "small cavities," regardless of the material used. 51 On the other hand, we found a similar percentage of restoration loss in each type of cavity (class I: 47%, class II: 53%), showing that this effect of the baseline characteristic on the fracture and retention rate in the materials seems irrelevant, at least in our study. Together with the treatment reason (carious lesion or restoration replacement), this showed a similar percentage of restoration loss between them (carious lesion: 49%, restoration replacement: 51%), which seems an unimportant factor in the restoration longevity.
However, a regression statistical analysis should be conducted in future studies to provide further evidence of the influence of those baseline characteristics' effect on restoration clinical performance.
One of the limitations of this study is that although some significant differences were observed between the groups after 24 months, which is a medium-term clinical follow-up, the defects observed did not impact the patients' perception and could be easily resolved by repolishing the restorations. 27 However, future studies with longer follow-ups need to be conducted to determine whether this difference can be confirmed.
Another limitation is that the number of restorations per patient showed some variability (three or more by each patient) due to the difficulty of recruiting patients with six restorations each, which is an ideal condition for this study. Although this is a common situation in the dental literature, 8 it may have caused a clustering effect, whose impact on the results was not considered and should be considered in future studies. However, 6% of all restorations in our study were inserted in patients with less than four teeth to be restored, which may have had a small impact on the present study's overall results.
Finally, the characteristics of the participants included in our study were good general health and acceptable oral hygiene, which could result in participants with low caries risk; therefore, a caries risk assessment was not conducted. However, a systematic analysis of participants' caries risk assessment would be important to identify patient factors' effect on restorations' clinical performance, 52 mainly if restorations performed in high-caries-risk patients showed a higher failure rate than those in low-risk patients. 53 Clinical studies should be conducted to evaluate bulk-fill composite restorations' performance, including the caries risk assessment to compare highand low-risk patients.

Conclusion
After 24 months of clinical service, all materials under investigation exhibited satisfactory restoration qualities.

Class I and II restorations performed with bulk-fill
composites showed similar survival rates regardless of the composite packaging and the use or non-use of SEE.
Restorations performed with bulk-fill composite in syringes presented fewer marginal defects than the composite applied with the incremental technique but more than those made with bulk-fill composite in capsules.

Restorations performed with SEE presented a
better marginal adaptation than those with the SET strategy.